Ebook Color atlas and text of histology (6th edition): Part 2

(BQ) Part 2 book Color atlas and text of histology presents the following contents: Endocrine system, integument, digestive system I, digestive system II, digestive system III, urinary system, female reproductive system, male reproductive system, special senses.

Graphic 10-2 Endocrine Glands p 238

Graphic 10-3 Sympathetic Innervation of the

Viscera and the Medulla of the Suprarenal Gland p 239

Tables

Table 10-1 Pituitary Gland Hormones

Table 10-2 Hormones of the Thyroid, Parathyroid,

Adrenal, and Pineal Glands

Plates

Plate 10-1 Pituitary Gland p 240

Fig 1 Pituitary gland

Fig 2 Pituitary gland Pars anterior

Fig 3 Pituitary gland Pars anterior

Plate 10-2 Pituitary Gland p 242

Fig 1 Pituitary gland

Fig 2 Pituitary gland Pars intermedia Human

Fig 3 Pituitary gland Pars nervosa

Fig 4 Pituitary gland Pars nervosa

Plate 10-3 Thyroid Gland, Parathyroid Gland p 244 Fig 1 Thyroid gland

Fig 2 Thyroid gland Fig 3 Thyroid and parathyroid glands Fig 4 Parathyroid gland

Plate 10-4 Suprarenal Gland p 246 Fig 1 Suprarenal gland Fig 2 Suprarenal gland Cortex Fig 3 Suprarenal gland Fig 4 Suprarenal gland Plate 10-5 Suprarenal Gland, Pineal Body

Fig 1 Suprarenal gland Cortex Fig 2 Suprarenal gland Medulla Fig 3 Pineal body Human Fig 4 Pineal body Human Plate 10-6 Pituitary Gland, Electron Microscopy

(EM) p 250 Fig 1 Pituitary gland Pars anterior (EM) Plate 10-7 Pituitary Gland, Electron Microscopy

(EM) p 251 Fig 1 Pituitary gland (EM) ENDOCRINE SYSTEM

T he endocrine system, in cooperation with the

nerv-ous system, orchestrates homeostasis by infl uencing, coordinating, and integrating the physiological func- tions of the body The endocrine system consists of several

glands, isolated groups of cells within certain organs, and

individual cells scattered among parenchymal cells of the

body This chapter considers only that part of the endocrine

system that is composed of glands Islets of Langerhans,

interstitial cells of Leydig, cells responsible for ovarian

hor-mone production, and DNES (diffuse neuroendocrine)

cells are treated in more appropriate chapters.

The endocrine glands to be discussed here are the

All of these glands produce hormones that they secrete

into the connective tissue spaces There are three types

of hormones, depending on how far they act from their

site of secretion:

• those that act on the cell, which releases them

• those that act in the immediate vicinity of their

secre-tion (paracrine hormones), and

• those that enter the vascular system and fi nd their

tar-get cells at a distance from their site of origin

This chapter details endocrine hormones (see Tables 10-1

and 10-2), whereas other chapters (nervous tissue,

res-piratory system, and digestive system) discuss autocrine

and paracrine hormones.

Some hormones (e.g., thyroid hormone) have a

gener-alized effect, in that most cells are affected by them; other

hormones (e.g., aldosterone) affect only certain cells.

within the cell are specifi c for a particular hormone.

• The binding of a hormone initiates a sequence of

reac-tions that results in a particular response.

• Because of the specifi city of the reaction, only a

minute quantity of the hormone is required.

• Some hormones elicit and others inhibit a particular

response.

Hormones, based on their chemical nature, are of three

types, nonsteroid, steroid based, and amino acid

deriva-tives Nonsteroid-based hormones (proteins and

and oxytocin) or small proteins (glucagon, insulin,

ante-rior pituitary proteins, and parathormone) Amino acid

hormone Steroid-based hormones and those of fatty acid

estrogen, progesterone, and testosterone).

Nonsteroid-Based Hormones and Amino Acid Derivatives

Nonsteroid-based endocrine hormones and amino acid

derivatives bind to receptors (some are G protein linked,

and some are catalytic) located on the target cell brane, activate them, and thus initiate a sequence of intracellular reactions These may act by

mem-• altering the state of an ion channel (opening or

closing) or

• by activating (or inhibiting) an enzyme or group of

enzymes associated with the cytoplasmic aspect of the cell membrane.

Opening or closing an ion channel will permit the ular ion to traverse or inhibit the particular ion from tra- versing the cell membrane, thus altering the membrane

partic-potential Neurotransmitters and catecholamines act on

ion channels.

• The binding of most hormones to their receptor will have only a single effect, which is the activation of

• This enzyme functions in the transformation of ATP to

cAMP (cyclic adenosine monophosphate), the major

a specifi c sequence of enzymes that are necessary to accomplish the desired result.

• There are a few hormones that activate a similar

com-pound, cyclic guanosine monophosphate (cGMP),

which functions in a comparable fashion.

Some hormones facilitate the opening of calcium

• calcium enters the cell, and three or four calcium ions

bind to the protein calmodulin, altering its conformation.

• The altered calmodulin is a second messenger that

acti-vates a sequence of enzymes, causing a specifi c response.

derivative and nonsteroid-based hormones, in that they

directly enter the nucleus, where they bind with

the activities of operators and/or promoters, resulting in

mRNA transcription The newly formed mRNAs enter the cytoplasm, where they are translated into proteins that elevate the cell’s metabolic activity.

Steroid-Based Hormones

tar-get cell through the plasma membrane and, once inside

the cell, bind to a receptor molecule.

TABLE 10-1 • Pituitary Gland Hormones

Pituitary Gland

Hormone

Inhibiting Hormone

Principal Functions

Pars distalis Somatotropin

(growth hormone [GH])

SRH Somatostatin Generally increases cellular metabolism;

stimulates liver to release insulin-like growth factors I and II resulting in cartilage proliferation and long bone growth

during pregnancy and production of milk after parturition

Adrenocorticotropic hormone (ACTH, corticotropin)

CRH Induces the zona fasciculata to synthesize and

secrete cortisol and corticosterone and cells

of the zona reticularis to synthesize and release androgens

Follicle-stimulating hormone (FSH)

LHRH Promotes ovulation, corpus luteum formation,

secretion of estrogen and progesterone in females

Interstitial stimulating hormone (ICSH)

cell-Promotes secretion of testosterone by Leydig cells in men

Thyroid-stimulating hormone (TSH;

thyrotropin)

TRH Stimulates secretion and release of

triiodothyro-nine and thyroxine by thyroid follicular cells

Pars nervosa Oxytocin Stimulates uterine smooth muscle contraction

during parturition Stimulates contractions of mammary gland myoepithelial cells during suckling

Vasopressin (antidiuretic hormone; ADH)

Elevates blood pressure by inducing vascular smooth muscle contraction, causes water resorption in collecting tubules of the kidney

• The receptor molecule-hormone complex enters the

nucleus, seeks out a specifi c region of the DNA

mol-ecule, and initiates the synthesis of mRNA.

• The newly formed mRNA codes for the formation

of specifi c enzymes that will accomplish the desired

result.

The presence of most hormones also elicits a vascularly

mediated negative feedback response, in that subsequent

to a desired response, the further production and/or

release of that particular hormone is inhibited.

PITUITARY GLAND

The pituitary gland (hypophysis) is composed of several

regions, namely, pars anterior (pars distalis), pars

tuber-alis, infundibular stalk, pars intermedia, and pars nervosa

(the last two are known as the pars posterior) (see Table

10-1 and Graphic 10-1).

Since the pituitary gland develops from two separate

embryonic origins, the epithelium of the pharyngeal roof

and the fl oor of the diencephalon, it is frequently

dis-cussed as being subdivided into two parts:

• the adenohypophysis (pars anterior, pars tuberalis,

and pars intermedia) and the

 The pars nervosa is continuous with the median

stalk (infundibular stalk).

The pituitary gland receives its blood supply from the

right and left superior hypophyseal arteries, serving the

median eminence, pars tuberalis, and the infundibulum,

and from the right and left inferior hypophyseal arteries,

which serve the pars nervosa.

hypo-physeal arteries give rise to the

median eminence.

plexus and deliver the blood into the secondary

• Both capillary plexuses are composed of fenestrated

Pars Anterior

The pars anterior is composed of numerous

parenchy-mal cells arranged in thick cords, with large capillaries

known as sinusoids, richly vascularizing the intervening

regions The parenchymal cells are classifi ed into two

main categories: those whose granules readily take up

stain, chromophils, and those cells that do not possess a strong affi nity for stains, chromophobes.

the classifi cation of these cells vis-à-vis their function,

it is probable that at least six of the seven hormones manufactured by the pars anterior are made by sepa- rate cells (see Table 10-1).

 Hormones that modulate the secretory functions of

the pituitary-dependent endocrine glands are

prolac-tin , adrenocorticotropin hormone (ACTH), and melanocyte-stimulating hormone (MSH).

 It is believed that two types of acidophils produce somatotropin and prolactin, whereas various pop- ulations of basophils produce the remaining fi ve hormones.

hormones They are believed to be acidophils and basophils that have released their granules.

• The axons of parvicellular, hypophyseotropic neurons whose soma are located in the paraventricular and arcuate nuclei of the hypothalamus terminate at the primary capillary bed.

 These axons store releasing hormones releasing hormone, prolactin-releasing hormone, corticotropin-releasing hormone, thyrotropin-releasing hormone, and gonadotropin-releasing hormone) and inhibitory hormones (prolactin-inhibiting hor- mone, inhibin, and somatostatin).

(somatotropin- The hormones are released by these axons into the primary capillary plexus and are conveyed to the secondary capillary plexus by the hypophyseal por- tal veins.

 The hormones then activate (or inhibit) chromophils

of the adenohypophysis, causing them to release or prevent them from releasing their hormones.

• An additional control is the mechanism of negative feedback, so that the presence of specifi c plasma levels

of the pituitary hormones prevents the chromophils from releasing additional quantities of their hormones.

Pars Intermedia The pars intermedia is not well developed It is believed that

the cell population of this region may have migrated into

the pars anterior to produce melanocyte-stimulating

that a single basophil can produce both of these hormones.

Pars Nervosa and Infundibular Stalk

• The pars nervosa does not present a very organized

appearance It is composed of pituicytes, cells believed

to be neuroglial in nature that may fulfi ll a supporting

function for the numerous unmyelinated axons of the

pars nervosa.

• These axons, whose cell bodies are located in the

hypo-thalamus, enter the pars nervosa via the

• Their axons possess expanded axon terminals, referred

to as Herring bodies, within the pars nervosa.

 Herring bodies contain oxytocin and antidiuretic

hormones that are stored in the pars nervosa but are

manufactured in the cell bodies in the hypothalamus.

 The release of these neurosecretory hormones

(neurosecretion) is mediated by nerve impulses

and occurs at the interface between the axon

ter-minals and the fenestrated capillaries.

 When the axon is ready to release its secretory

products, the pituicytes withdraw their processes

and permit the secretory product a clear access to

the capillaries.

Pars Tuberalis

The pars tuberalis is composed of numerous cuboidal

cells whose function is not known.

THYROID GLAND

The thyroid gland consists of right and left lobes that are

interconnected by a narrow isthmus across the thyroid

cartilage and upper trachea (see Table 10-2 and Graphic

10-2) It is enveloped by a connective tissue capsule

whose septa penetrate the substance of the gland,

form-ing not only its supportform-ing framework but also its conduit

for its rich vascular supply.

The parenchymal cells of the gland are arranged in

numerous follicles, composed of a simple cuboidal

secreted and resorbed by the follicular cells, is composed

of thyroid hormone that is bound to a large protein, and

the complex is known as thyroglobulin.

To synthesize thyroid hormone

follicular cells at their basal aspect via iodide pumps.

• Iodide is oxidized by thyroid peroxidase on the apical

cell membrane and is bound to tyrosine residues of

thyroglobulin molecules.

• Within the colloid, the iodinated tyrosine residues

become rearranged to form triiodothyronine (T3) and

To release thyroid hormone

• The binding of thyroid-stimulating hormone (TSH)

released by the pituitary, to receptors on the basal aspect of their plasmalemma induces follicular cells to become tall cuboidal cells.

• They form pseudopods on their apical cell membrane

that engulf and endocytose colloid.

• The colloid-fi lled vesicles fuse with lysosomes, and T3and T4 residues are removed from thyroglobulin, liber-

ated into the cytosol, and are released at the basal aspect

of the cell into the perifollicular capillary network.

• Thyroid hormone (see Table 10-2) is essential for ulating basal metabolism and for infl uencing growth rate and mental processes and generally stimulates endocrine gland functioning.

reg-An additional secretory cell type, parafollicular cells (clear

with the colloidal material They manufacture the hormone

tissue in the immediate vicinity of capillaries Calcitonin (see Table 10-2) helps control calcium concentrations in the blood by inhibiting bone resorption by osteoclasts (i.e., when blood calcium levels are high, calcitonin is released).

Parathyroid Glands

The parathyroid glands, usually four in number, are

embedded in the fascial sheath of the posterior aspect of the thyroid gland They possess slender connective tissue capsules from which septa are derived to penetrate the glands and convey a vascular supply to the interior In the adult, two types of parenchymal cells are present in the parathyroid glands:

• numerous small chief cells and a smaller number of

• large acidophilic cells, the oxyphils.

Fatty infi ltration of the glands is common in older als Although there is no known function of oxyphils, chief

individu-cells produce parathyroid hormone (PTH see Table 10-2).

main-taining proper calcium ion balance.

• The concentration of calcium ions is extremely tant in the normal function of muscle and nerve cells and

impor-as a releimpor-ase mechanism for neurotransmitter substance.

• A drop in blood calcium concentration activates a back mechanism that stimulates chief cell secretion.

feed-• PTH binds to receptors on osteoblasts that release osteoclast-stimulating factor followed by bone

resorption and a consequent increase in blood calcium

ion concentration.

 In the kidneys, PTH prevents urinary calcium loss;

thus, ions are returned to the bloodstream.

 PTH also controls calcium uptake in the

intes-tines indirectly by modulating kidney tion of vitamin D, which is essential for calcium absorption.

produc-Increased levels of PTH cause an elevation in plasma

cal-cium concentration; however, it takes several hours for

this level to peak The concentration of PTH in the blood

is also controlled by plasma calcium levels.

• Unlike PTH, calcitonin is fast acting, and since it binds

directly to receptors on osteoclasts, it elicits a peak

reduction in blood calcium levels within one hour.

• Calcitonin inhibits bone resorption, thus reducing

cal-cium ion levels in the blood High levels of calcal-cium

ions in the blood stimulate calcitonin release.

Absence of parathyroid glands is not compatible with life.

Suprarenal Glands

The suprarenal glands (adrenal glands in some

ani-mals) are invested by a connective tissue capsule (see

Table 10-2 and Graphics 10-2 and 10-3) The glands are

derived from two different embryonic origins, namely,

and neuroectoderm, from which the medulla originates

The rich vascular supply of the gland is conveyed to the

interior in connective tissue elements derived from the

capsule.

Cortex

The cortex is subdivided into three concentric regions

or zones that secrete specifi c hormones (see Table 10-2)

Control of these hormonal secretions is mostly regulated

by ACTH from the pituitary gland.

• The outermost region, just beneath the capsule, is

the zona glomerulosa, where the cells are arranged in

arches and spherical clusters with numerous

capillar-ies surrounding them.

 Cells of the zona glomerulosa secrete aldosterone,

a mineralocorticoid that acts on cells of the tal convoluted tubules of the kidney to modulate water and electrolyte balance.

dis-• The second region, the zona fasciculata, is the most

extensive Its parenchymal cells, usually known as

numer-ous capillaries between the cords.

• Zona fasciculata cells secrete cortisol and corticosterone.

 These glucocorticoids regulate carbohydrate lism, facilitate the catabolism of fats and proteins, exhibit anti-infl ammatory activity, and suppress the immune response.

metabo-• The innermost region of the cortex, the zona

rich intervening capillary network.

 Zona reticularis cells secrete weak androgens that

promote masculine characteristics.

Medulla Parenchymal cells of the medulla, derived from neural

crest material, are disposed in irregularly arranged short cords surrounded by capillary networks They contain numerous granules that stain intensely when the freshly cut tissue is exposed to chromium salts This is referred

to as the chromaffi n reaction, and the cells are called

chromaf-fi n cells that secrete the two hormones (see Table 10-2)

of the suprarenal medulla, mainly

Secretion of these two catecholamines is directly lated by preganglionic fi bers of the sympathetic nervous system that impinge on the postganglionic sympathetic neuron-like chromaffi n cells, which are considered to

regu-be related to postganglionic sympathetic neurons (see Graphic 10-3) Catecholamine release occurs in physi- cal and psychological stress Moreover, scattered, large

act on smooth muscle cells of the medullary veins, thus controlling blood fl ow in the cortex.

Pineal Body

The pineal body (epiphysis) is a projection of the roof of

the diencephalon (see Table 10-2 and Graphic 10-2) The connective tissue covering of the pineal body is pia mater, which sends trabeculae and septa into the substance of the pineal body, subdividing it into incomplete lobules Blood vessels, along with postganglionic sympathetic nerve fi bers from the superior cervical ganglia, travel in these connective tissue elements As the nerve fi bers enter the pineal body, they lose their myelin sheath The parenchyma of the pin- eal body is composed of pinealocytes and neuroglial cells.

• The pinealocytes form communicating junctions with each other and manufacture melatonin Interestingly,

melatonin is manufactured only at night.

sup-port to pinealocytes.

• The pineal body receives indirect input from the ina , which allows the pineal to differentiate between

ret-TABLE 10-2 • Hormones of the Thyroid, Parathyroid, Adrenal, and Pineal Glands

Promotes gene transcription and lates carbohydrate and fat metabolism

stimu-Increases basal metabolism, growth rates, endocrine gland secretion, heart rate, and respiration Decreases cho-lesterol, phospholipid, and triglyceride levels and lowers body weight

Calcitonin (thyrocalcitonin)

Lowers blood calcium levels by ing osteoclastic activity

suppress-Parathyroid gland Parathyroid hormone Increases blood calcium levels

Angiotensin II and adrenocorticotropic hormone (ACTH)

Stimulates distal convoluted tubules of the kidney to resorb sodium and excrete potassium

and corticosterone)

ACTH Controls carbohydrate, lipid, and protein

metabolism Stimulates esis Reduces infl ammation and sup-presses the immune system

(dehydroepian-drosterone and androstenedione)

ACTH No signifi cant effect in a healthy individual

Medulla Catecholamines

(epinephrine and norepinephrine)

Preganglionic sympathetic and splanchnic nerves

Epinephrine—increases blood pressure and heart rate, promotes glucose release

by the liverNorepinephrine—elevates blood pressure via vasoconstriction

Pineal body

(pineal gland)

Melatonin Norepinephrine Infl uences the individual’s diurnal rhythm

day and night, and, in that manner, assists in the

estab-lishment of the circadian rhythm.

• The extracellular spaces of the pineal body

con-tain calcifi ed granular material known as brain sand

(corpora arenacea), whose signifi cance, if any, is not

known.

It is unclear how the pineal gland functions in humans, but it does exert an affect on the control of the circadian rhythm Nonetheless, melatonin is used to treat jet lag and in regulating emotional responses related to short-

ened daylight during winter, a condition called seasonal

Pituitary Gland

breast milk or a woman who is not breast-feeding

pro-duces breast milk In men, it is often accompanied by

impotence, headache, and loss of peripheral vision

and in women by hot fl ashes, vaginal dryness, and

an abnormal menstrual cycle This rather uncommon

condition is usually a result of prolactinoma, a tumor

of prolactin-producing cells of the pituitary gland The

condition is usually treated by drug intervention or

sur-gery, or both.

the pregnancy-induced enlarging of the pituitary

gland and its concomitant increase in its

vascular-ity The high vascularity of the pituitary increases the

chances of a vascular accident, such as hemorrhage,

which results in the partial destruction of the pituitary

gland The condition may be severe enough to

pro-duce Sheehan’s syndrome, which is recognized by the

lack of milk production, the loss of pubic and axillary

hair, and fatigue.

Pituitary Somatotrope Adenoma

adenomas, benign tumors, that are more common in

adults than in children Somatotrope adenomas involve

proliferation of acidophils, which produce an excess of

growth hormones which, in children, result in

gigan-tism , whereas in adults it results in acromegaly These

acidophils grow slowly and usually do not grow outside

the sella turcica Individuals affl icted with untreated

acromegaly frequently suffer from complications that increase their chance of succumbing to cardiovascular, cerebrovascular, and respiratory problems These indi- viduals also present with hypertension.

Thyroid Gland

antibodies to TSH receptors thus stimulating increased

thy-roid hormone production (hyperthythy-roidism) Clinically,

the thyroid gland becomes enlarged, and there is dence of exophthalmic goiter (protrusion of the eyeballs).

evi-CLINICAL CONSIDERATIONS

This is a photomicrograph from the pituitary gland of a patient with pituitary somatotrope adenoma Note that the adenoma cells are arranged in ribbons and cords (Reprinted with permission from Rubin R, Strayer D, et al., eds Rubin’s Pathology Clinicopathologic Foundations of Medicine, 5th ed Baltimore: Lippincott Williams &

Wilkins, 2008, p 938.)

Parathyroid Gland

benign tumor causing the excess production of parathyroid

hormone (PTH) The high levels of circulating PTH cause

increased bone resorption with a resultant greatly elevated

blood calcium The excess calcium may become deposited

in arterial walls and in the kidneys, creating kidney stones.

Suprarenal Gland

it may also be the aftermath of tuberculosis It is

characterized by decreased production of adrenocortical hormones due to the destruction of the suprarenal cor- tex, and without the administration of steroid treatment,

it may have fatal consequences.

disor-der, affects the thyroid and suprarenal glands in such a fashion that they are underactive (although the thyroid may become overactive) Frequently, patients with this disorder also develop diabetes.

This photomicrograph of the adrenal gland of a patient with Addison’s disease displays cortical fi brosis and infl ammation,

as well as a mass of atrophic cortical cells (Reprinted with mission from Rubin R, Strayer D, et al., eds Rubin’s Pathology

per-Clinicopathologic Foundations of Medicine, 5th ed Baltimore:

Lippincott Williams & Wilkins, 2008, p 962.)

This photomicrograph is from the thyroid gland of a patient with

Graves’ disease Note that the follicular cells are high columnar

hyperplastic cells enclosing pinkish colloid that is scalloped along its

periphery (Reprinted with permission from Rubin R, Strayer D, et al.,

eds Rubin’s Pathology Clinicopathologic Foundations of Medicine,

5th ed Baltimore: Lippincott Williams & Wilkins, 2008, p 946.)

Supraopticnuclei

Secretion

TSH

Thyroid

SecretionFSH

Testis

genesis

Spermato-AndrogensecretionLH

Ovary

Folliculardevelopment:

estrogensecretion

Ovulation:

progesteronesecretion

ProlactinMammary gland

Milksecretion

Growth hormonevia insulin-like growth factors

I and II

AdiposetissueElevation

of freefatty acids

MuscleHyper-

glycemia

BoneGrowth

Mammarygland

Myoepithelialcontraction

OxytocinUterus

KidneyWater absorption

Parsnervosa

Hypophysealstalk

Medianeminence

Growth hormonevia insulin-like growth factors

I and II

GRAPHIC 10-2 •

Thyroid Gland

Follicularcell

Parafollicularcell

Parathyroid Gland

Oxyphil cell

Chief cell

Capsule

Suprarenal Gland

CortexMedulla

Capsule

Neuroglialcell

Sympatheticchain ganglionCollateral

ganglion

Medulla of suprarenal gland

Ventral rootganglion

Stomach, small intestine, large intestine

Thoracicspinal cord

This survey photomicrograph of the pituitary gland demonstrates

the relationship of the gland to the hypothalamus (H), from

which it is suspended by the infundibulum The infundibulum is

composed of a neural portion, the infundibular stem (IS) and the

surrounding pars tuberalis (PT) Note that the third ventricle

(3V) of the brain is continuous with the infundibular recess (IR)

The largest portion of the pituitary is the pars anterior (PA), which

is glandular and secretes numerous hormones The neural

com-ponent of the pituitary gland is the pars nervosa (PN), which does

not manufacture its hormones but stores and releases them Even

at this magnifi cation, its resemblance to the brain tissue and to

the substance of the infundibular stalk is readily evident Between

the pars anterior and pars nervosa is the pars intermedia (PI),

which frequently presents an intraglandular cleft (IC), a remnant

of Rathke’s pouch

section ×132.

The pars anterior is composed of large cords of cells that branch

and anastomose with each other These cords are surrounded

by an extensive capillary network However, these capillaries are

wide, endothelially lined vessels known as sinusoids (S) The

parenchymal cells of the anterior pituitary are divided into two

groups: chromophils (Ci) and chromophobes (Co) With

hema-toxylin and eosin, the distinction between chromophils and mophobes is obvious The former stain blue or pink, whereas the

chro-latter stain poorly The boxed area is presented at a higher

magni-fi cation in Figure 3

section ×270.

This is a higher magnification of the boxed area of Figure 2

Note that the chromophobes (Co) do not take up the stain well and only their nuclei (N) are demonstrable These cells are

small; therefore, chromophobes are easily recognizable since their nuclei appear to be clumped together The chromophils may be classified into two categories by their affinity to his-

tologic dyes: blue-staining basophils (B) and pink-colored acidophils (A) The distinction between these two cell types in sections stained with hematoxylin and eosin is not as apparent

as with some other stains Note also the presence of a large

Hypothalamus

Infundibular stemPars intermediaPars anterior

BasophilAcidophil

Parsnervosa

PN PA

PI IC

IR

IS

FIGURE 1

It is somewhat diffi cult to discriminate between the acidophils (A)

and basophils (B) of the pituitary gland stained with hematoxylin

and eosin Even at high magnifi cation, such as in this

photomicro-graph, only slight differences are noted Acidophils stain pinkish and

are slightly smaller in size than the basophils, which stain pale blue

In a black and white photomicrograph, basophils appear darker

than acidophils Chromophobes (Co) are readily recognizable, since

their cytoplasm is small and does not take up stain Moreover, cords

of chromophobes present clusters of nuclei (N) crowded together.

section ×132.

The pars nervosa of the pituitary gland is composed of

elon-gated cells with long processes known as pituicytes (P), which

are thought to be neuroglial in nature These cells, which

pos-sess more or less oval nuclei, appear to support numerous

unmy-elinated nerve fi bers traveling from the hypothalamus via the

hypothalamo-hypophyseal tract These nerve fi bers cannot be

distinguished from the cytoplasm of pituicytes in a hematoxylin

and eosin–stained preparation Neurosecretory materials pass

along these nerve fi bers and are stored in expanded regions at the

termination of the fi bers, which are then referred to as Herring

bodies (HB) Note that the pars nervosa resembles neural tissue

The boxed area is presented at a higher magnifi cation in Figure 4.

Paraffi n section ×270.

The pars intermedia of the pituitary gland is situated between the

pars anterior (PA) and the pars nervosa (PN) It is characterized

by basophils (B), which are smaller than those of the pars rior Additionally, the pars intermedia contains colloid (Cl)-fi lled

ante-follicles, lined by pale, small, low cuboidal-shaped cells (arrows)

Note that some of the basophils extend into the pars nervosa

Numerous blood vessels (BV) and pituicytes (P) are evident in

this area of the pars nervosa

section ×540.

This photomicrograph is a higher magnifi cation of the boxed area

of Figure 3 Note the numerous more or less oval nuclei (N) of the

pituicytes, some of whose processes (arrows) are clearly evident at

this magnifi cation The unmyelinated nerve fi bers and processes

of pituicytes make up the cellular network of the pars nervosa The expanded terminal regions of the nerve fi bers, which house neu-

rosecretions, are known as Herring bodies (HB) Also observe the presence of blood vessels (BV) in the pars nervosa.

Parsnervosa }

Chromophobes}

Pituitary gland

The capsule of the thyroid gland sends septa of connective tissue

into the substance of the gland, subdividing it into incomplete

lobules This photomicrograph presents part of a lobule

display-ing many follicles (F) of varied sizes Each follicle is surrounded by

slender connective tissue (CT), which supports the follicles and

brings blood vessels (BV) in close approximation The follicles are

composed of follicular cells (FC), whose low cuboidal

morphol-ogy indicates that the cells are not producing secretory product

During the active secretory cycle, these cells become taller in

mor-phology In addition to the follicular cells, another parenchymal

cell type is found in the thyroid gland These cells do not border the

colloid, are located on the periphery of the follicles, and are known

as parafollicular cells (PF) or C cells They are large and possess

centrally placed round nuclei, and their cytoplasm appears paler

Plastic section ×132.

Although the parathyroid (PG) and thyroid glands (TG) are

sepa-rated by their respective capsules (Ca), they are extremely close

to each other The capsule of the parathyroid gland sends

trabec-ulae (T) of connective tissue carrying blood vessels (BV) into the

substance of the gland The parenchyma of the gland consists of

two types of cells, namely, chief cells (CC), also known as principal

cells, and oxyphil cells (OC) Chief cells are more numerous and

possess darker staining cytoplasm Oxyphil cells stain lighter and

are usually larger than chief cells, and their cell membranes are

evident A region similar to the boxed area is presented at a higher

magnifi cation in Figure 4

×540.

The thyroid follicle (F) presented in this photomicrograph is rounded by several other follicles and intervening connective tis- sue (CT) Nuclei (N) in the connective tissue may belong either

sur-to endothelial cells or sur-to connective tissue cells Since most illaries are collapsed in excised thyroid tissue, it is often diffi cult

cap-to identify endothelial cells with any degree of certainty The licular cells (FC) are fl attened, indicating that these cells are not actively secreting thyroglobulin Note that the follicles are fi lled

fol-with a colloid (Cl) material Observe the presence of a licular cell (PF), which may be distinguished from the surround-

parafol-ing cells by its pale cytoplasm (arrow) and larger nucleus.

section ×540.

This photomicrograph is a region similar to the boxed area of

Figure 3 The chief cells (CC) of the parathyroid gland form small cords surrounded by slender connective tissue (CT) elements and blood vessels (BV) The nuclei (N) of connective tissue cells

may be easily recognized due to their elongated appearance

Oxyphil cells (OC) possess a paler cytoplasm, and frequently, the

cell membranes are evident (arrows) The glands of older

individu-als may become infi ltrated by adipocytes

The suprarenal gland, usually embedded in adipose tissue (AT), is

invested by a collagenous connective tissue capsule (Ca) that

pro-vides thin connective tissue elements that carry blood vessels and

nerves into the substance of the gland Since the cortex (Co) of

the suprarenal gland completely surrounds the fl attened medulla

(M), it appears duplicated in any section that completely transects

the gland The cortex is divided into three concentric regions:

the outermost zona glomerulosa (ZG), middle zona

fascicu-lata (ZF), and the innermost zona reticularis (ZR) The medulla,

which is always bounded by the zona reticularis, possesses several

large veins (V), which are always accompanied by a considerable

amount of connective tissue

section ×132.

The columnar arrangement of the cords of the zona fasciculata

(ZF) is readily evident by viewing the architecture of the blood

vessels indicated by the arrows The cells in the deeper region of

the ZF are smaller and appear denser than the more superfi cially

located spongiocytes (Sp) Cells of the zona reticularis (ZR) are

arranged in irregular, anastomosing cords whose interstices

con-tain wide capillaries The cords of the ZR merge almost

impercep-tibly with those of the ZF This is a relatively narrow region of the

cortex The medulla (M) is clearly evident since its cells are much

larger than those of the ZR Moreover, numerous large veins (V)

are characteristic of the medulla

section ×132.

The collagenous connective tissue capsule (Ca) of the suprarenal gland is surrounded by adipose tissue through which blood ves- sels (BV) and nerves (Ne) reach the gland The parenchymal cells

of the cortex, immediately deep to the capsule, are arranged in

an irregular array, forming the more or less oval to round clusters

or arch-like cords of the zona glomerulosa (ZG) The cells of the zona fasciculata (ZF) form long, straight columns of cords ori-ented radially, each being one to two cells in width These cells are larger than those of the ZG They present a vacuolated appear-ance due to the numerous lipid droplets that were extracted dur-

ing processing and are often referred to as spongiocytes (Sp) The interstitium is richly vascularized by blood vessels (BV).

section ×540.

The capsule (Ca) of the suprarenal gland displays its collagen

fi bers (Cf) and the nuclei (N) of the fi broblasts The zona merulosa (ZG), which occupies the upper part of the photomi-

glo-crograph, displays relatively small cells with few vacuoles (arrows)

The lower part of the photomicrograph demonstrates the zona fasciculata (ZF), whose cells are larger and display a more vacuo-

lated (arrowheads) appearance Note the presence of connective

tissue (CT) elements and blood vessels (BV) in the interstitium

between cords of parenchymal cells

Z reticularis

Z fasciculata

Z glomerulosaCapsule

The upper part of this photomicrograph presents the border

between the zona fasciculata (ZF) and the zona reticularis (ZR)

Note that the spongiocytes (Sp) of the fasciculata are larger and

more vacuolated than the cells of the reticularis The parenchymal

cells of the zona reticularis are arranged in haphazardly

anasto-mosing cords The interstitium of both regions houses large

capil-laries containing red blood cells (RBC) Inset Zona fasciculata

Monkey Plastic section ×540 The spongiocytes (Sp) of the

zona fasciculata are of two different sizes Those positioned more

superfi cially in the cortex, as in this inset, are larger and more

vac-uolated (arrows) than spongiocytes close to the zona reticularis.

section ×132.

The pineal body is covered by a capsule of connective tissue

derived from the pia mater From this capsule, connective tissue

trabeculae (T) enter the substance of the pineal body,

subdivid-ing it into numerous incomplete lobules (Lo) Nerves and blood

vessels (BV) travel in the trabeculae to be distributed throughout

the pineal, providing it with a rich vascular supply In addition to

endothelial and connective tissue cells, two other types of cells

are present in the pineal, namely, the parenchymal cells, known

as pinealocytes (Pi), and neuroglial supporting cells (Ng) A

characteristic feature of the pineal body is the deposit of calcifi ed

material known as corpora arenacea or brain sand (BS) The boxed

area is presented at a higher magnifi cation in Figure 4

Plastic section ×270.

The cells of the adrenal medulla, often referred to as chromaffi n cells (ChC), are arranged in round to ovoid clusters or in irregularly arranged short cords The cells are large and more or less round

to polyhedral in shape with a pale cytoplasm (Cy) and vesicular appearing nucleus (N), displaying a single, large nucleolus (n)

The interstitium presents large veins (V) and an extensive lary (Cp) network Large ganglion cells are occasionally noted

section ×540.

This photomicrograph is a higher magnifi cation of the boxed area

of Figure 3 With the use of hematoxylin and eosin stain, only the nuclei of the two cell types are clearly evident The larger,

paler, more numerous nuclei belong to the pinealocytes (Pi)

The smaller, denser nuclei are those of the neuroglial cells (Ng)

The pale background is composed of the long, intertwining cesses of these two cell types The center of the photomicrograph

pro-is occupied by brain sand (BS) Observe that these concretions

increase in size by apposition of layers on the surface of the

calci-fi ed material, as may be noted at the arrow.

Z reticularis

Z fasciculata

Z glomerulosaCapsule

Spongiocytes

Neuroglial cell

Pineal body

Although considerable controversy surrounds the precise fi ne

structural identifi cation of the cells of the pars anterior, it is

rea-sonably certain that the several cell types presented in this

elec-tron micrograph are acidophils, basophils, and chromophobes, as

observed by light microscopy The acidophils are somatotropes (S) and mammotropes (M), whereas only two types of basophils are included in this electron micrograph, namely, type II gonado- tropes (G2) and thyrotropes (T) The chromophobes (C) may

be recognized by the absence of secretory granules in their plasm (From Poole M Cellular distribution within the rat adeno-hypophysis: a morphometric study Anat Rec 1982;204:45–53.)

cyto-FIGURE 1

The pars distalis of the rat pituitary houses various cell types, two

of which are represented here The granule-containing

gonado-trophs (GN) are surrounded by nongranular folliculostellate cells

(FS), whose processes are demarcated by arrows The functions of

folliculostellate cells are in question, although some believe them

to be supportive, phagocytic, regenerative, or secretory in nature (From Strokreef JC, Reifel CW, Shin SH A possible phagocytic role for folliculo-stellate cells of anterior pituitary following estrogen with-drawal from primed male rats Cell Tissue Res 1986;243:255–261.)

FIGURE 1

Chapter Summary

Endocrine glands are characterized by the absence

of ducts and the presence of a rich vascular network

The parenchymal cells of endocrine glands are usually

arranged in short cords, follicles, or clusters, although

other arrangements are also common.

I PITUITARY GLAND

The pituitary gland is invested by a connective tissue

Stain pink with hematoxylin and eosin They are found

mostly in the center of the pars anterior.

2 Basophils

Stain darker than acidophils with hematoxylin and eosin

They are more frequently found at the periphery of the

pars anterior.

b Chromophobes

granular and has very little affi nity for stain They may

be recognized as clusters of nuclei throughout the pars

anterior.

B Pars Intermedia

The pars intermedia is rudimentary in man Small

baso-phils are present as well as colloid-fi lled follicles.

C Pars Nervosa and Infundibular Stalk

These have the appearance of nervous tissue The cells

of the pars nervosa are pituicytes, resembling neuroglial

cells They probably support the unmyelinated nerve fi

b-ers , whose terminal portions are expanded, since they

store neurosecretions within the pars nervosa These

expanded terminal regions are known as Herring bodies.

D Pars Tuberalis

The pars tuberalis is composed of cuboidal cells arranged

in cords They may form small colloid-fi lled follicles.

II THYROID GLAND

A Capsule

The capsule of the thyroid gland consists of a thin

the substance of the gland, subdividing it into lobules.

B Parenchymal Cells

The parenchymal cells of the thyroid gland form

periph-ery of the follicles

The gland is invested by a slender collagenous connective

tissue capsule from which septa arise to penetrate the

substance of the gland.

B Parenchymal Cells

1 Chief Cells

that form cords.

2 Oxyphils

num-ber than chief cells.

C Connective Tissue

Collagenous connective tissue septa as well as slender

IV SUPRARENAL GLAND

The suprarenal gland is invested by a collagenous nective tissue capsule The gland is subdivided into a cor- tex and a medulla.

con-A Cortex

The cortex is divided into three concentric zones: zona

1 Zona Glomerulosa

The zona glomerulosa is immediately deep to the

cap-sule It consists of columnar cells arranged in arches and

spherical clusters.

2 Zona Fasciculata

The thickest zone of the cortex is the zona fasciculata The

more or less cuboidal cells (spongiocytes) are arranged

in long, parallel cords Spongiocytes appear highly

vacu-olated except for those of the deepest region, which are

smaller and much less vacuolated.

3 Zona Reticularis

The innermost zone of the cortex is the zona reticularis It

is composed of small, dark cells arranged in irregularly

anas-tomosing cords The intervening capillaries are enlarged.

B Medulla

The medulla is small in humans and is composed of large,

granule-containing chromaffi n cells arranged in short

cords Additionally, large autonomic ganglion cells are

also present A characteristic of the medulla is the ence of large veins.

Characteristic of the pineal body are the calcifi ed

accre-tions in the extracellular spaces, known as brain sand or

11

CHAPTER OUTLINE

Graphics

Graphic 11-1 Skin and Its Derivatives p 262

Graphic 11-2 Hair, Sweat Glands, and Sebaceous

Glands p 263

Tables

Table 11-1 Characteristics of Thick and Thin Skin

Table 11-2 Nonepithelial Cells of the Epidermis

Plates

Plate 11-1 Thick Skin p 264

Fig 1 Thick skin

Fig 2 Thick skin

Fig 3 Thick skin

Fig 4 Thick skin

Plate 11-2 Thin Skin p 266

Fig 1 Thin skin Human

Fig 2 Thin skin Human Fig 3 Thin skin Human Plate 11-3 Hair Follicles and Associated Structures,

Sweat Glands p 268 Fig 1 Hair follicle Human l.s.

Fig 2 Hair follicle Human x.s.

Fig 3 Sebaceous gland Human Fig 4 Sweat gland

Plate 11-4 Nail, Pacinian and Meissner’s Corpuscles

Fig 1 Sweat gland Human (EM) x.s.

INTEGUMENT

T he integument, the largest and heaviest organ of

the body, is composed of skin and its various atives, including sebaceous glands, sweat glands, hair, and nails The skin covers the entire body and is con-

deriv-tinuous with the mucous membranes at the lips, at the

anus, in the nose, at the leading edges of the eyelids, and

at the external orifi ces of the urogenital system Some of

the many functions of skin include

• protection against physical, chemical, and biologic

assaults;

• providing a waterproof barrier;

• absorbing ultraviolet radiation for both vitamin D

syn-thesis and protection;

• excretion (i.e., sweat) and thermoregulation;

• monitoring the external milieu via its various nerve

endings;

• and immunologic defense of the body.

SKIN

Skin is composed of a superfi cial stratifi ed squamous

connective tissue layer, the dermis (see Graphic 11-1—

please note that free nerve endings are not depicted in this

diagram).

• The epidermis and dermis interdigitate with each

other by the formation of epidermal ridges and

sepa-rated by a basement membrane.

 Frequently, a dermal ridge is subdivided into two

secondary dermal ridges with an intervening papillary peg from the epidermis.

inter-• The ridges on the fi ngertips that imprint as fi

nger-prints are evidence of this interdigitation.

Interposed between skin and deeper structures is a

fas-cial sheath known as the hypodermis, which is not a part

of skin.

Skin can be classifi ed as thick or thin depending on the

thickness of its epidermis and of its dermis Since it is the

thickness of the epidermis that is usually obvious when

viewed with the microscope, the epidermis of thick skin

is presented here The epidermis of skin can be thick, as

on the sole of the foot and the palm of the hand, or thin,

as over the remainder of the body (see Table 11-1).

The epidermis of

basale, stratum spinosum, stratum granulosum, stratum lucidum, and stratum corneum.

gran-ulosum and stratum lucidum are absent as defi ned layers However, individual cells of the two absent layers are present even in thin skin.

well-Epidermis of Thick Skin

The epidermis is composed of four cell types, cytes, melanocytes, Langerhans cells, and Merkel cells Approximately 95% of the cells of the epidermis are keratinocytes, and it is their morphology that is responsi- ble for the characteristics of the fi ve layers.

keratino-Keratinocytes and the Five Layers of the Epidermis The deepest layer of the epidermis, the stratum basale

(formerly known as stratum germinativum), is a gle layer of cuboidal to columnar cells These cells are responsible for cell renewal, via mitosis (usually at night), and the newly formed cells are pushed surfaceward, giv- ing rise to the thickest layer, the stratum spinosum.

sin- The cuboidal/columnar cells sit on a basement

dermis, and form hemidesmosomes with the basal lamina and desmosomal contacts with each other and

with the basal-most cells of the stratum spinosum.

 These cells of the stratum basale form keratin 5 and

 Cells, mostly in the deeper layer of the stratum spinosum, also display mitotic activity (usually at night).

 These prickle cells form keratin 1 and keratin

10 that replace keratins 5 and 14 formed by the

stratum basale The keratins are intermediate

 These prickle cells in the superfi cial layers of the stratum spinosum also form

structures that are composed of lin and fi laggrin These two proteins, associ-

trichohya-ated with intermediate fi laments, promote

the keratin fi laments into thick bundles of tonofi laments.

are composed of ceramides, phospholipids, and glycosphingolipids.

• Continuous migration of the cells of the stratum

spi-nosum forms the next layer, the stratum granulosum.

 Cells of this layer accumulate more

destroying their nuclei and organelles.

TABLE 11-1 • Characteristics of Thick and Thin Skin

Cellular Strata

(Superfi cial to deepest)

consist of four cell types: keratinocytes, melanocytes, Langerhans cells, and Merkel cells

Stratum corneum

(Cornifi ed cell layer)

Composed of several layers of dead, anucleated,

fl attened keratinocytes (squames) that are being sloughed from the surface As many as

50 layers of keratinocytes are located in the thickest skin (e.g., sole of the foot)

Only about fi ve or so layers of keratinocytes (squames) comprise this layer in the thinnest skin (e.g., eyelids)

Stratum lucidum

(Clear cell layer)

Poorly stained keratinocytes fi lled with keratin compose this thin, well-defi ned layer Organelles and nuclei are absent

Layer is absent but individual cells of the layer are probably present

Stratum granulosum

(Granular cell layer)

Only three to fi ve layers thick with polygonal-shaped nucleated keratinocytes with a normal complement of organelles

as well as keratohyalin and membrane-coating granules

Layer is absent but individual cells of the layer are probably present

Stratum spinosum

(prickle cell layer)

This thickest layer is composed of mitotically active and maturing polygonal keratino-cytes (prickle cells) that interdigitate with one another via projections (intercellular bridges) that are attached to each other by desmosomes The cytoplasm

is rich in tonofi laments, organelles, and membrane-coating granules Langerhans cells are present in this layer

This stratum is the same as in thick skin but the number of layers is reduced

fi cial strata originate from this layer and eventually migrate to the surface where they are sloughed Melanocytes and Merkel cells are also present in this layer

This layer is the same in thin skin as in thick skin

is derived from mesoderm and is composed mostly of dense irregular collagenous tive tissue It contains capillaries, nerves, sensory organs, hair follicles, sweat and sebaceous glands, as well as arrector pili muscles It is divided into two layers: a superfi cial papillary layer and a deeper reticular layer

connec-Papillary layer Is comprised of loose connective tissue

containing capillary loops and terminals of mechanoreceptors These dermal papillae interdigitate with the epidermal ridges of the epidermis These interdigitations are very prominent in thick skin

The papillary layer is comprised of the same loose connective tissue as in thick skin However, its volume is much reduced The depth of the dermal/epidermal interdigitations is also greatly reduced

Reticular layer Is composed of dense irregular collagenous

connective tissue containing the usual array

of connective tissue elements, including cells, blood, and lymphatic vessels

Sweat glands and cutaneous nerves are also present and their branches extend into the papillary layer and into the epidermis

Same as in thick skin with the addition of

Sebaceous glands and hair follicles along with their arrector pili muscles are observed

 Cells of the stratum granulosum also continue to

manufacture membrane-coating granules.

 Cells of the stratum granulosum contact each other

via desmosomes and, in their superfi cial layers, also

form claudin-containing occluding junctions with

each other as well as with cells of the stratum dum (or, in the absence of the stratum lucidum, with the stratum corneum).

luci- In the superfi cial layers, cells of the stratum

granulo-sum release the contents of their membrane- coating granules into the extracellular space These cells no longer contain organelles or a nucleus and are con-

sidered to be dead having undergone apoptosis.

 The stratum spinosum and stratum granulosum

together are frequently referred to as the stratum Malpighii.

• The fourth layer, the stratum lucidum, is relatively

thin and is usually absent in thin skin When evident in

thick skin, palmar and plantar skin, it usually appears

as a thin, translucent region, interposed between the

strata granulosum and the corneum.

 The cells of the stratum lucidum have no nuclei or

organelles but contain a large amount of tonofi brils embedded in keratohyalin.

• The surface-most layer is the stratum corneum,

com-posed of preferentially arranged stacks of dead hulls

known as squames.

 The squames, similar to the cells of the stratum

luci-dum, are fi lled with the keratohyalin-keratin plex, which deposits on the internal aspect of the

com-cell membrane, forming a cornifi ed com-cell envelope.

 The cornifi ed cell envelope is further buttressed

by at least three proteins, involucrin, loricrin, and

 The contents of the Odland bodies, released by

cells of the strata spinosum and granulosum, form

a lipid envelope that provides a waterproof barrier.

 The cornifi ed cell envelope and the lipid envelope

form a structure known as the compound cornifi ed

 The superfi cial layers of the stratum corneum are

desquamated at the same rate as they are being replaced by the mitotic activity of the strata basale and spinosum while maintaining the integrity of the compound cornifi ed cell envelope.

Recent investigations indicate that keratinocytes

pro-duce immunogenic molecules and are probably active

in the immune process Evidence also shows that these

cells are capable of producing several interleukins,

colony-stimulating factors, interferons, tumor necrosis

factors, as well as platelet- and fi broblast-stimulating

growth factors.

Nonkeratinocytes of the Epidermis

There are three types of nonkeratinocytes in the dermis: melanocytes, Langerhans cells, and Merkel cells (see Table 11-2).

epi-Melanocytes

Melanoblasts, derived from neural crest cells,

differenti-ate into melanocytes under the infl uence of the signaling molecule stem cell factor Melanocytes manufacture a dark melanin pigment.

epidermis during embryonic development and lish residence in the forming stratum basale and may establish hemidesmosomes with the basal lamina Some of the premelanocytes differentiate into mel- anocytes, whereas other remain in an undifferentiated state even in the adult.

estab-• Once there, they do not make desmosomal contact

with other cells in their vicinity but form long

pro-cesses, dendrites, that penetrate the stratum spinosum.

• Each melanocyte forms an association, via its drites, with a number of keratinocytes, referred to as

• The number of keratinocytes per melanocyte varies with regions of the body but is relatively constant across the races, and approximately 3% of the cells of the epidermis consist of melanocytes.

In the adult premelanocytes enter into the cell cycle to maintain their population as well as to differentiate into melanocytes.

• The hormone a-MSH binds to melanocortin tors on the melanocyte cell membrane that acti- vates a cAMP pathway prompting the melanocyte to

recep-express microphthalmia-associated transcription tor (MITF).

fac- MITF not only regulates the mitotic activity of the premelanocytes but also induces the formation of melanin, in specialized organelles of melanocytes

known as melanosomes.

There are two types of melanin, eumelanin, a dark

brown to black pigment composed of polymers of

compound composed of cysteinyl dopa polymers.

• Eumelanin is present in individuals with dark hair.

• Pheomelanin is found in individuals with red and blond hair.

Both types of melanin are derived from the amino acid

tyrosinase-containing vesicles derived from the trans-Golgi network,

known as premelanosomes.

• Within these oval (1.0 by 0.5 mm) premelanosomes,

mela-nin (melanofi laments).

• As the amount of melanin increases within the

pre-melanosomes, its fi lamentous structure is no longer

evident, and the organelles mature into much darker

structures known as melanosomes.

• Melanosomes possess the transmembrane protein

• Melanosomes travel, along microtubules powered by

• The Rab27a binds a cytoplasmic molecule,

 permits a detachment of the melanosome from the

kinesin and

 facilitates its attachment to myosin Va, which

trans-fers the melanosome to F-actin

 melanosomes are transported to the immediate

vicinity of the dendrite plasmalemma along the

F-actin pathway.

 Myosin Va detaches from the F-actin and permits

the exocytosis of the melanosome into the

extracel-lular space.

Once melanosomes enter the extracellular space,

keratinocytes of the stratum spinosum phagocytose

them The melanosomes migrate to the nuclear region of

the keratinocyte and form a protective umbrella,

shield-ing the nucleus (and its chromosomes) from the

ultravio-let rays of the sun Soon thereafter, lysosomes attack and

destroy the melanosomes.

• Ultraviolet rays not only increase the rates of

darken-ing of melanin and endocytosis of the melanosomes

but also enhance tyrosinase activity and thus melanin

production.

• Fewer melanocytes are located on the insides of the

thighs and undersides of the arms and face Skin

pig-mentation is related to the location of melanin rather

than to the numbers of melanocytes.

• Melanosomes are fewer and congregate around the

keratinocyte nucleus in Caucasians, whereas in

dark-skinned individuals they are larger and are more

dis-persed throughout the keratinocyte cytoplasm The

destruction of the melanosomes occurs at a slower

rate in darker than in lighter skin.

Langerhans Cells

their long processes) are derived from bone marrow and

located mostly in the stratum spinosum They function

as antigen-presenting cells in immune responses The

nucleus of these cells possesses numerous indentations, and their cytoplasm contain, in addition to the usual

organelles, Birbeck granules, elongated vesicles whose

end is ballooned Langerhans cells:

• do not make desmosomal contact with the cells of the stratum spinosum.

• express CD1a surface marker and MHC I, MHC II, Fc

transmem-brane protein langerin that is associated with Birbeck

granules Langerin and CD1a facilitate the immune

defense against Mycobacterium leprae, the

microorgan-ism responsible for leprosy

includ-ing nonprotein antigens.

When a Langerhans cell phagocytoses an antigen, the cell migrates into a lymph vessel of the dermis to enter the paracortex of a nearby lymph node Here, the Langerhans cell presents its antigen to T cells to activate

a delayed-type hypersensitivity response.

Merkel Cells

authors believe them to be a modifi ed type of cyte, are interspersed among the cells of the stratum basale and are most abundant in the fi ngertips Afferent nerve terminals approximate these cells, forming com- plexes, known as Merkel discs that are believed to func-

keratino-tion as mechanoreceptors (touch receptors) There is

some evidence that Merkel cells may also have a secretory function.

neuro-Dermis The dermis of the skin, lying directly deep to the epi-

dermis, is derived from mesoderm It is composed of

mostly type I collagen and numerous elastic fi bers that

assist in securing the skin to the underlying hypodermis.

• The dermis is subdivided into a loosely woven

ridges), a superfi cial region that interdigitates with the epidermal ridges (and interpapillary pegs) of the epi- dermis, and

• a deeper, coarser, and denser reticular layer The

interface between the papillary and reticular layers is indistinct.

display encapsulated nerve endings, such as Meissner’s

nour-ishment to the avascular epidermis.

embryonic development Some remain undifferentiated even in adulthood (reserved to maintain melanocyte population) Do not form desmosomal contact with keratinocytes but some may form hemidesmosomes with basal lamina.

pass into the stratum spinosum Melanocytes possess melanosomes within their cytoplasm where mela- nin is manufactured Melanocytes form associations with several keratinocytes (epidermal-melanin unit) Population = to about 3% of epidermal population

located in the cytoplasm are activated to produce melanin (eumelanin in dark hair and pheomelanin in red and blond hair)

travel up the dendrites and are released into the extracellular space Keratinocytes of the stratum spinosum phagocytose these melanin-laden melanosomes The melanosomes migrate to the nuclear region of the keratinocyte and form a protective umbrella, shielding the nucleus (and its chromosomes) from the ultraviolet rays of the sun Soon, the melanosomes are destroyed by keratinocyte lysosomes

congregate around the nucleus, whereas in dark-skinned individuals, they are larger and

Melanosome destruction is at a slower pace in darker skin

they are known as dendritic cells Nucleus

Are antigen-presenting cells These cells possess surface markers and receptors

as well as langerin, a transmembrane protein associated with Birbeck granules Some of these elements facilitate an immune response against the organism responsible for leprosy

antigens that enter the epidermis and migrate to lymph vessels located in the dermis and from there into the paracortex of a lymph node to present these antigens to T cells, thereby acti- vating a delayed-type hypersensitivity response

although origin is uncertain

of the stratum basale They are most abundant in the fi

as Merkel discs, with terminals of afferent nerves

DERIVATIVES OF SKIN

Derivatives of skin include hair, sebaceous glands, sweat

glands, and nails (see Graphic 11-2) These structures

originate from epidermal downgrowths into the dermis

and hypodermis, while maintaining their connection to

the outside.

• Each hair is composed of a shaft of cornifi ed cells and

a root contained within a hair follicle

 is associated with a sebaceous gland that secretes

an oily sebum into the neck of the hair follicle.

 A small bundle of smooth muscle cells, the arrector

cradling the sebaceous gland, inserts into the superfi

-cial aspects of the skin.

follicles These are simple, coiled, tubular glands whose secretory units produce sweat, which is delivered to the surface of the skin by long ducts.

of these glands.

each fi nger and toe These horny plates lie on a nail bed and are bounded laterally by a nail wall.

 The cuticle (eponychium) lies over the lunula, an

opaque, crescent-shaped area of the nail plate.

 The hyponychium is located beneath the free edge

of the nail plate.

CLINICAL CONSIDERATIONS

This photomicrograph is of a patient suffering from psoriasis garis Note that the stratum spinosum and stratum corneum are thickened and that the stratum granulosum is absent The pap-illary layer of the dermis displays an infi ltration by lymphocytes

vul-(Reprinted with permission from Mills SE, Carter D, et al., eds

Sternberg’s Diagnostic Surgical Pathology, 5th ed., Philadelphia, Lippincott, Williams & Wilkins, 2010, p 6.)

Itching (Pruritis)

The sensation of itching is accompanied by an

instinc-tive, almost irrepressible urge to scratch There are many

different causes of itching, some as simple as a fl y

walk-ing on one’s skin and movwalk-ing the hair follicles, or as

seri-ous as debilitating systemic conditions such as kidney

failure or liver disease If the itching is accompanied by

a rash, then the probable cause is not the kidney or the

liver Parasitic infestations (mites, scabies, etc.), insect

bites, plant toxins (such as poison oak and poison ivy),

and drug allergies are usually accompanied by a rash and

require medical intervention If the itching is long-term,

the patient should seek the assistance of a physician

Pregnancy and cold, dry weather may also be

contribut-ing factors to itchcontribut-ing.

Psoriasis Vulgaris

characterized by reddish patchy lesions on the skin

with grayish sheen, located especially around joints,

sacral region, the navel, and the scalp This condition

is produced by increased proliferation of keratinocytes

and an acceleration of the cell cycle, resulting in an

accumulation of cells in the stratum corneum but with

an absence of a stratum granulosum and, frequently,

the presence of lymphocytic infiltrates in the papillary

layer The condition is cyclic and is of unknown

etiology.

Erythema Multiforme

Patches of elevated red skin, frequently resembling a get, displaying a symmetrical distribution over the face and extremities, that occurs periodically indicate the disorder erythema multiforme It is most frequently due

tar-to herpes simplex infection The condition is not usually

accompanied by itching, although painful lesions

(blis-ters) on the lips and buccal cavity are common

occur-rences Usually the condition resolves itself, but in more

severe cases, medical intervention is indicated.

Warts

Warts are benign epidermal growths on the skin caused

by papilloma viral infection of the keratinocytes Warts

are common in young children, in young adults, and in

immunosuppressed patients.

Vitiligo

A condition in which the skin has patches of white areas

due to the lack of pigmentation is known as vitiligo

The melanocytes of the affected region are destroyed

in an autoimmune response The condition may appear

suddenly after a physical injury or as a consequence

of sunburn If the area affected has hair, as the hair

grows it will be white Although there are no physical

consequences to vitiligo, there may be psychological

sequelae.

Malignancies of Skin

The three most common malignancies of skin are basal

cell carcinoma, squamous cell carcinoma, and malignant

melanoma.

malignancy, develops in the stratum basale from

CLINICAL CONSIDERATIONS

This photomicrograph is of a patient with basal cell carcinoma

Note that the lesion is composed of dark, dense basal cells that form

rounded nodules that are separated from the dermal connective

tissue by narrowed spaces (Reprinted with permission from Mills

SE, Carter D, et al., eds Sternberg’s Diagnostic Surgical Pathology,

5th ed., Philadelphia, Lippincott, Williams & Wilkins, 2010 p 49.)

damage caused by ultraviolet radiation The foremost

type of basal cell carcinoma is the nodulocystic type

where small hyperchromatic cells form spherical ules that are separated from the surrounding connec- tive tissue elements of the dermis by narrow spaces

nod-The most frequent site of basal cell carcinoma is on the nose, occurring as papules or nodules, which eventu- ally craters Surgery is usually 90% effective with no recurrence.

skin malignancy, is invasive and metastatic Its probable etiology is environmental factors, such as ultraviolet radi- ation and x-irradiation, as well as a variety of chemical carcinogens, including arsenic The carcinoma originates

in cells of the stratum spinosum and appears clinically

as a hyperkeratotic, scaly plaque with deep invasion of underlying tissues, often accompanied by bleeding

Surgery is the treatment of choice.

malignancy It develops in the epidermis where nocytes become mitotically active and form a dysplastic

mela-nevus It may then enter a radial-growth phase where

individual melanocytes invade the dermis, then enter the

in the dermis, and eventually become a full-fl edged,

lymphatic and circulatory system to metastasize to other organ systems.

This photomicrograph is of a patient suffering from malignant melanoma Note that the melanocytes are invading the dermis

in large numbers, indicating that the melanoma is in the vertical growth phase (Reprinted with permission from Mills SE, Carter

D, et al., eds Sternberg’s Diagnostic Surgical Pathology, 5th ed., Philadelphia, Lippincott, Williams & Wilkins, 2010 p 92.)

Hair shaft Sebaceous (oil) gland Arrector pili muscle

Eccrine sweat gland Apocrine sweat gland

Hair follicle

Hair root

Pacinian corpuscle Artery Vein Adipose tissue of hypodermis

Dermis

Eccrine sweat gland

Stratum spinosum

Stratum corneum

Epidermis

Skin and its appendages, hair, sweat glands (both eccrine and apocrine), sebaceous glands, and nails, are known

as the integument Skin may be thick or thin, depending on the thickness of its epidermis Thick skin epidermis is composed of five distinct layers of keratinocytes (strata basale, spinosum, granulosum, lucidum, and corneum) interspersed with three additional cell types, melanocytes, Merkel’s cells, and Langerhans’ cells Thin skin

epidermis lacks strata granulosum and lucidum, although individual cells that constitute the absent layers are present.

Stratum lucidum Stratum granulosum

Langerhans’ cell Merkel cell Melanocyte Basement membrane Blood vessel Stratum basale

Sebaceous glands are

branched acinar holocrine glands whose short ducts empty into a hair follicle into the space created by the disappearance of the internal root sheath.

Secretory components of

eccrine sweat glands

consist of simple cuboidal epithelium composed of

dark cells, clear cells, and myoepithelial cells The ducts of these glands are

composed of a stratified cuboidal (two layers of cuboidal cells) epithelium.

Huxley’s layer Henle’s layer

External root sheath Glassy membrane Root hair plexus

Duct of sebaceous gland

Hair shaft

Hair papilla

Hair Root

Free edge Nail body Lunula Cuticle Nail root

Pore

Excretory duct

Eccrine Sweat Gland

Myoepithelial cell Dark cell Clear cell

Secretory portion

Sebaceous cell

Sebaceous Gland

Hair follicle

Skin is composed of the superfi cial epidermis (E) and the deeper

dermis (D) The interface of the two tissues is demarcated by

epi-dermal ridges (ER) and dermal ridges (DR) (dermal papillae)

Between successive epidermal ridges are the interpapillary pegs,

which divide each dermal ridge into secondary dermal ridges

Note that in thick skin the keratinized layer, stratum corneum

(SC), is highly developed Observe also that the duct (d) of the

sweat gland pierces the base of an epidermal ridge The dermis

of skin is subdivided into two regions, a papillary layer (PL),

com-posed of the looser, collagenous connective tissue of the dermal

ridges, and the deeper, denser, collagenous connective tissue of

the reticular layer (RL) Blood vessels (BV) from the reticular layer

enter the dermal ridges

This is a higher magnifi cation of a region similar to the boxed area

in the previous fi gure The papillary layer (PL) of the dermis

dis-plays nuclei (N) of the various connective tissue cells as well as

the interface between the dermis and the stratum basale (SB)

Observe that these cells are cuboidal to columnar in shape, and

interspersed among them are occasional clear cells, probably

inac-tive melanocytes (M), although it should be stressed that Merkel

cells also appear as clear cells Cells of the stratum spinosum

(SS) are polyhedral in shape, possessing numerous intercellular

bridges, which interdigitate with those of other cells, accounting

for their spiny appearance

This photomicrograph of thick skin presents a view similar to that

in Figure 1 However, the layers of the epidermis (E) are much ier to delineate in this plastic section Observe that the squames

eas-of the stratum corneum (SC) appear to lie directly on the tum granulosum (SG), whose cells contain keratohyalin granules

stra-The thickest layer of lining cells in the epidermis is the stratum spinosum (SS), whereas the stratum basale (SB) is only a single

cell layer thick The stratum lucidum is not evident, although a few

transitional cells (arrows) may be identifi ed Note that the

second-ary dermal ridges (SDR), on either side of the interpapillary peg

(IP), present capillary loops (CL) Regions similar to the boxed

This is a higher magnifi cation of a region similar to the boxed area

of Figure 2 Observe that as the cells of the stratum spinosum (SS) are being pushed surfaceward, they become somewhat fl attened

As the cells reach the stratum granulosum (SG), they

accumu-late keratohyalin granules (arrows), which increase in number

as the cells progress through this layer Occasional transitional

cells (arrowheads) of the poorly defi ned stratum lucidum may be

observed as well as the squames (S) of the stratum corneum (SC)

displays the stratum lucidum (SL) to advantage Note that this layer is between the stratum granulosum (SG) and stratum cor- neum (SC) Observe the duct (d) of a sweat gland.

SS

SG S

SC

SC

SG SL

d

Thin skin is composed of a very slender layer of epidermis (E) and

the underlying dermis (D) Although thick skin has no hair follicles

and sebaceous glands associated with it, most thin skin is richly

endowed with both Observe the hair (H) and the hair follicles (HF),

whose expanded bulb (B) presents the connective tissue papilla

(P) Much of the follicle is embedded beneath the skin in the

super-fi cial fascia, the fatty connective tissue layer known as the

hypo-dermis (hD), which is not a part of the integument Sebaceous

glands (sG) secrete their sebum into short ducts (d), which empty

into the lumen of the hair follicle Smooth muscle bundles,

arrec-tor pili muscle (AP), cradle these glands, in passing from the hair

follicle to the papillary layer of the dermis Sweat glands (swG) are

also present in the reticular layer of the dermis A region similar to

the boxed area is presented at a higher magnifi cation in Figure 2.

This is a higher magnifi cation of a region similar to the boxed area

of the previous fi gure Observe that the epidermis (E) is much

thinner than that of thick skin and that the stratum corneum (SC)

is signifi cantly reduced The epidermal ridges and interpapillary

pegs (IP) are well represented in this photomicrograph Note that

the papillary layer (PL) of the dermis is composed of much fi ner

bundles of collagen fi bers (CF) than those of the dense irregular

collagenous connective tissue of the reticular layer (RL) The

der-mis is quite vascular, as evidenced by the large number of blood

vessels (BV) whose cross-sectional profi les are readily observed

The numerous nuclei (N) of the various connective tissue cells

attest to the cellularity of the dermis Note also the presence of the

arrector pili muscle (AP), whose contraction elevates the hair and

is responsible for the appearance of “goose bumps.” The boxed

area is presented at a higher magnifi cation in the following fi gure

Stratum basalePapillary layerSebaceous glandHair follicleHair bulb

Sweat glandHypodermis

DermisEpidermis

This photomicrograph is a higher magnifi cation of the boxed area

of Figure 2 Epidermis of thin skin possesses only three of four of the layers found in thick skin The stratum basale (SB) is present

as a single layer of cuboidal to columnar cells Most of the

epi-dermis is composed of the prickle cells of the stratum spinosum

(SS), whereas stratum granulosum and stratum lucidum are not represented as complete layers However, individual cells of stra-

tum granulosum (arrow) and stratum lucidum are scattered at the

interface of the stratum spinosum and stratum corneum (SC)

The papillary layer of the dermis (D) is richly vascularized by illary loops (CL), which penetrate the secondary dermal ridges (sDR) Observe that the collagen fi ber (CF) bundles of the dermis

cap-become coarser as the distance from the epidermis increases

AP arrector pili muscle

FIGURE 2

SC

SS sDR

SB CL

D CF

FIGURE 3